Alkaline phosphatase and prognosis in patients with coronary artery disease

Ndrepepa, Gjin; Xhepa, Erion; Braun, Siegmund; Cassese, Salvatore; Fusaro, Massimiliano; Schunkert, Heribert; Kastrati, Adnan

doi:10.1111/eci.12752

Cited by 38 publications

(30 citation statements)

References 28 publications

(54 reference statements)

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“…Another question is whether the local or systemic TNAP activity drives vascular calcification. Epidemiological studies clearly show that increased blood alkaline phosphatase activity correlates with coronary artery calcification [15, 16]. Therefore, it is plausible that circulating enzyme can be deposited into vascular tissues to increase calcification.…”

Section: Discussionmentioning

confidence: 99%

“…Increased TNAP expression has also been detected in patients suffering from vascular calcification associated with diabetes [12] and chronic kidney disease [13, 14]. Recent epidemiological studies point to a potential pathophysiological role and a prognostic value of increased blood alkaline phosphatase activity in human coronary artery disease [15, 16]. …”

Section: Introductionmentioning

confidence: 99%

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Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

et al. 2017

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ObjectiveOverexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium.Approach and resultsA vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study. Endothelial overexpression of TNAP was achieved in mice harboring a homozygous recessive mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2-cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery calcification at baseline compared WHC controls (4312 vs 0μm2 alizarin red area, p<0.001). Eight weeks after induction of atherosclerosis, lipid deposition in the coronary arteries of WHC-eTNAP was increased compared to WHC controls (121633 vs 9330μm2 oil red O area, p<0.05). Coronary lesions in WHC-eTNAP mice exhibited intimal thickening, calcifications, foam cells, and necrotic cores. This was accompanied by the reduction in body weight and left ventricular ejection fraction (19.5 vs. 23.6g, p<0.01; 35% vs. 47%, p<0.05). In a placebo-controlled experiment under atherogenic conditions, pharmacological inhibition of TNAP in WHC-eTNAP mice by a specific inhibitor SBI-425 (30mg*kg-1*d-1, for 5 weeks) reduced coronary calcium (78838 vs.144622μm2) and lipids (30754 vs. 77317μm2); improved body weight (22.4 vs.18.8g) and ejection fraction (59 vs. 47%). The effects of SBI-425 were significant in the direct comparisons with placebo but disappeared after TNAP-negative placebo-treated group was included in the models as healthy controls.ConclusionsEndogenous TNAP activity is present in human cardiac tissues. TNAP overexpression in vascular endothelium in mice leads to an unusual course of coronary atherosclerosis, in which calcification precedes lipid deposition. The prevalence and significance of this mechanism in human atherosclerosis requires further investigations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

et al. 2017

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“…They found that ALP was an independent predictor of adverse outcomes among 4115 participants with a previous myocardial infarction 11. This observation then was verified and extended by other researches that elevated ALP was an independent predictor of adverse outcomes in patients with CAD,12 13 ACS14 15 and STEMI 16 17. However, no study focuses on the prognostic value of ALP for in-hospital mortality in patients with ACS undergoing PCI.…”

Section: Discussionmentioning

confidence: 85%

Prognostic impact of alkaline phosphatase for in-hospital mortality in patients with acute coronary syndrome: a prospective cohort study in China

et al. 2019

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ObjectivesAlkaline phosphatase (ALP) can promote vascular calcification, but the association between ALP and in-hospital mortality in patients with acute coronary syndrome (ACS) is not well defined.DesignA prospective cohort study.Setting and participantsA total of 6368 patients with ACS undergoing percutaneous coronary intervention (PCI) from 1 January 2010 to 31 December 2017 were analysed.Main outcome measuresIn-hospital mortality was used in this study.ResultsALP was analysed both as a continuous variable and according to three categories. After multivariable adjustment, in-hospital mortality was significantly higher in Tertile 3 group (ALP＞85 U/L) (OR: 2.399, 95% CI 1.080 to 5.333, p=0.032), compared with other two groups (Tertile 1: ＜66 U/L; Tertile 2: 66–85 U/L). When ALP was evaluated as a continuous variable, after multivariable adjustment, the ALP level was associated with an increased risk of in-hospital mortality (OR: 1.011, 95% CI 1.002 to 1.020, p=0.014). C-statistic of ALP for predicting in-hospital mortality was 0.630 (95% CI 0.618 to 0.642, p=0.001). The cut-off value was 72 U/L with a sensitivity of 0.764 and a speciﬁcity of 0.468. However, ALP could not significantly improve the prognostic performance of Global Registry of Acute Coronary Events (GRACE) score (GRACE score+ALP vs GRACE score: C-statistic: z=0.485, p=0.628; integrated discrimination improvement: 0.014, p=0.056; net reclassification improvement: 0.020, p=0.630).ConclusionsIn patients with ACS undergoing PCI, ALP was an independent predictor of in-hospital mortality. But it could not improve the prognostic performance of GRACE score.

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“…Opposite to PTH, an association of serum osteocalcin with cardiovascular death is unclear, being U-shaped as well as gender-and age-dependent [31][32][33]. Data regarding the prognostic significance of alkaline phosphatase are also contradictory, varying between revascularisation modalities [34][35][36]. Albeit serum alkaline phosphatase may be also increased in patients with stroke, chronic heart failure, arterial hypertension, type 2 diabetes mellitus, and obesity, a number of studies showed its usefulness as a prognostic indicator during the long-term follow-up of patients with coronary artery disease [35,36] including those with ST-segment elevation MI [37].…”

Section: Discussionmentioning

confidence: 99%

“…Data regarding the prognostic significance of alkaline phosphatase are also contradictory, varying between revascularisation modalities [34][35][36]. Albeit serum alkaline phosphatase may be also increased in patients with stroke, chronic heart failure, arterial hypertension, type 2 diabetes mellitus, and obesity, a number of studies showed its usefulness as a prognostic indicator during the long-term follow-up of patients with coronary artery disease [35,36] including those with ST-segment elevation MI [37]. In addition, SAP of CCS grade IV, New York Heart Association class IV chronic heart failure, and obesity were among the criteria of exclusion in our study.…”

Section: Discussionmentioning

confidence: 99%

Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery

et al. 2019

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Despite the fact that an association of osteopoenia/osteoporosis with elevated risk of coronary artery calcification (CAC) and coronary atherosclerosis (CA) is well-established, it remains unclear whether bone turnover markers can be employed in long-term prognostication of such patients. Here we measured serum calcium, phosphate, calcitonin, parathyroid hormone (PTH), osteoprotegerin, osteocalcin, osteopontin, alkaline phosphatase and its bone isoenzyme, subsequently correlating them with an adverse cardiovascular outcome after 3 years of follow-up. The extent of brachiocephalic artery stenosis, CA, or CAC, as well as prevalence of osteopoenia/osteoporosis before the coronary artery bypass graft (CABG) surgery, did not differ between outcome groups, suggesting that subtle molecular mechanisms might be involved in determining the outcome rather than clinical or subclinical disease. After stepwise logistic regression, serum osteocalcin > 26.8 ng/mL and PTH > 49.1 pg/mL were independent predictors of an adverse outcome. Serum ionised calcium correlated with multivessel coronary artery disease; moreover, patients with severe CA (SYNTAX score > 21) had higher serum ionised calcium than those with mild CA. Likewise, serum alkaline phosphatase was associated with severe CA and CAC (Agatston score > 400). In conclusion, serum PTH, osteocalcin, and alkaline phosphatase are associated with an adverse cardiovascular outcome 3 years after CABG surgery regardless of osteopoenia/osteoporosis, coronary/peripheral atherosclerosis, and CAC.

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Alkaline phosphatase and prognosis in patients with coronary artery disease

Abstract: Background The evidence on the association between alkaline phosphatase (ALP) and prognosis of patients with coronary artery disease (CAD) is limited. The aim of this study was to assess the association of ALP with the risk of mortality or coronary events in patients with CAD.

Cited by 38 publications

References 28 publications

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia

Prognostic impact of alkaline phosphatase for in-hospital mortality in patients with acute coronary syndrome: a prospective cohort study in China

Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery

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